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dc.contributor.authorLi, Xiaofei
dc.contributor.authorZhao, Jing
dc.contributor.authorKasinath, Vivek
dc.contributor.authorUehara, Mayuko
dc.contributor.authorJiang, Liwei
dc.contributor.authorBanouni, Naima
dc.contributor.authorMcGrath, Martina M
dc.contributor.authorIchimura, Takaharu
dc.contributor.authorFiorina, Paolo
dc.contributor.authorLemos, Dario R
dc.contributor.authorShin, Su Ryon
dc.contributor.authorWare, Carl F
dc.contributor.authorBromberg, Jonathan S
dc.contributor.authorAbdi, Reza
dc.date.accessioned2020-08-13T18:32:44Z
dc.date.available2020-08-13T18:32:44Z
dc.date.issued2020-08-03
dc.identifier.urihttp://hdl.handle.net/10713/13548
dc.description.abstractAlthough the immune response within draining lymph nodes (DLNs) has been studied for decades, how their stromal compartment contributes to this process remains to be fully explored. Here, we show that donor mast cells were prominent activators of collagen I deposition by fibroblastic reticular cells (FRCs) in DLNs shortly following transplantation. Serial analysis of the DLN indicated that the LN stroma did not return to its baseline microarchitecture following organ rejection and that the DLN contained significant fibrosis following repetitive organ transplants. Using several FRC conditional-knockout mice, we show that induction of senescence in the FRCs of the DLN resulted in massive production of collagen I and a proinflammatory milieu within the DLN. Stimulation of herpes virus entry mediator (HVEM) on FRCs by its ligand LIGHT contributed chiefly to the induction of senescence in FRCs and overproduction of collagen I. Systemic administration of ex vivo-expanded FRCs to mice decreased DLN fibrosis and strengthened the effect of anti-CD40L in prolonging heart allograft survival. These data demonstrate that the transformation of FRCs into proinflammatory myofibroblasts is critically important for the maintenance of a proinflammatory milieu within a fibrotic DLN.en_US
dc.description.urihttps://doi.org/10.1172/JCI136618en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society of Clinical Oncologyen_US
dc.relation.ispartofJournal of Clinical Investigationen_US
dc.subjectFibrosisen_US
dc.subjectImmunologyen_US
dc.subjectOrgan transplantationen_US
dc.subjectTherapeuticsen_US
dc.titleLymph node fibroblastic reticular cells deposit fibrosis-associated collagen following organ transplantationen_US
dc.typeArticleen_US
dc.identifier.doi10.1172/JCI136618
dc.identifier.pmid32597832
dc.source.volume130
dc.source.issue8
dc.source.beginpage4182
dc.source.endpage4194
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


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